The pharmacokinetics and bacteriological efficacy of nafcillin (NFPC), vancomycin (VCM), amikacin (AMK) and rifampicin (RFP) alone and in VCM combinations were evaluated in the experimental rabbit meningitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) or methicillin-resistant Staphylococcus aureus (MRSA). The mean concentrations of NFPC, VCM, AMK and RFP in cerebrospinal fluid (CSF) with MSSA meningitis exceeded the minimal bactericidal concentrations of MSSA during 8 hours therapy period. The mean CSF penetration rates of the 4 drugs during therapy were from 1% to 26% which are comparable to those observed in humans with meningitis. The median CSF bactericidal titers of RFP, VCM plus RFP, AMK, VCM plus AMK regimens were larger than 1:8 during therapy of MSSA meningitis study. In experimental MRSA meningitis, RFP and VCM plus RFP achieved titers greater than 1: 16 during therapy and at 24 hours. No statistically significant reduction in the CSF bacterial colony count was obtained with any of the antibiotic regimens in MSSA meningitis. By contrast, in 8 hours MRSA meningitis model, significant reductions in the number of MRSA were observed in animals treated for 8 hours with VCM plus RFP (P less than 0.01), RFP (P less than 0.05), and NFPC plus RFP (P less than 0.01).